A new ink-jet oligonucleotide array synthesizer and several novel applications of this technology are being developed by the Institution for Systems Biology (ISB). When completed, specifications for construction, maintenance, and operation of this unique system will be released to the scientific community, satisfying the need for fast, flexible, and inexpensive synthesis of custom oligonucleotide array chips. Preliminary experiments comparing the results from ink-jet and pin-spotted microarrays for halobacterium, yeast, and murine T-cell receptor model systems reveal significant progress in the development of the ISB ink-jet arrayer. Despite considerable improvements, better consistency, density, and improved quality controls of in situ oligonucleotide synthesis are needed before this instrument is ready to be introduced into basic research laboratories. The most promising advantage of in situ ink-jet array synthesis over alternative methods is its speed and flexibility; new arrays can be designed and printed overnight without the need to catalog and array thousands of PCR gene products. We intend to take advantage of this flexibility to approach new challenges. In addition to gene expression analysis, we will adapt ink-jet chips to study the effects of gene knock-outs and synthetic lethal mutations, genetic variation, in vitro transcription factor binding, and in vivo protein binding to native chromatin. Because improved integration of oligonucleotide design, data acquisition, analysis, and the ability to share data with other laboratories must assume a high priority in today's post-genomic research setting, we are developing software that can quickly find unique oligonucleotides for hundreds or thousands of genes or DNA segments simultaneously. This software is being integrated into a relational database package utilizing emerging MIAME/MAGE standards for microarray data. Data from other high-throughput techniques, such as DNA sequencing, genotyping, and proteomics, can be ported into this system, and links to analysis software developed at the ISB or at other institutions will be incorporated. The goal of this project is to make a fast, flexible ink-jet array system available to the scientific community and to provide software that enhances the functionalities of the system through quality control, data collection and analysis, and graphic visualization of the complex data-sets generated by the arrayer.